The introduction of the tetrazine-based inverse electron demand Diels-Alder (iEDDA) reaction was a major breakthrough in bioorthogonal chemistry (see, e.g., Blackman, M. L. et al., J. Am. Chem. Soc. 2008, 130, 13518-13519; and Devaraj, N. K. et al., Bioconjugate Chem. 2008, 19, 2297-2299). The stability of the reaction partners and the excellent kinetics, in particular when employing trans-cyclooctene as the dienophile, has made these reagents a useful tool for bioorthogonal labeling experiments (see, e.g., Blackman, M. L. et al., J. Am. Chem. Soc. 2008, 130, 13518-13519; and Devaraj, N. K. et al., Bioconjugate Chem. 2008, 19, 2297-2299; Rossin, R. et al., Angew. Chem. Int. Ed. 2010, 49, 3375-3378; Devaraj, N. K. and Weissleder, R. Acc. Chem. Res. 2011, 44, 816-827; and Keliher, E. et al., ChemMedChem 2011, 6, 424-427). Early research on this cycloaddition chemistry focused on optimization of the cycloaddition reaction kinetics via modification of tetrazine. More recently, additional trans-cyclooctene derivatives with significantly improved cycloaddition kinetics have been reported (see, e.g., Blackman, M. L. et al., J. Am. Chem. Soc. 2008, 130, 13518-13519; and Devaraj, N. K. et al., Bioconjugate Chem. 2008, 19, 2297-2299), but at the expense of decreased chemical stability or significantly increased molecular weight of the reactants.